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Tuesday, June 15, 2010

Repeat after us: Correlation is not causation, correlation is not causation, correlation is not....

Confounding is probably the single most important explanation for irreproducible and even nonsensical results in epidemiology--and probably in genetics and evolutionary reconstructions as well. In the mid 1900's, for example, before everyone had telephones, researchers found that having a phone was a risk factor for breast cancer. How could that be? As it turned out, having a phone was associated with middle or upper class status, and money was associated with a diet that included increasingly more fat--or with increased age at first birth, or fewer children, and so on--risk factors for breast cancer subsequently identified by many studies that noted increased risk as socioeconomic status rose. Confounding is notoriously difficult to control, largely because many associations can't be anticipated in advance of the design of a study. (Whether the same-sounding argument applies to the idea that use of cell phones 'causes' brain cancer is not known.)

The BBC is reporting that meat eating causes early menarche. Or rather, eating a lot of meat. This according to a paper in Public Health Nutrition (though this is only the latest of the papers reporting this correlation). The age at menarche--first menstrual period--dropped throughout the 20th century and many people have wondered why. It had been thought that this was due to increased nutrition in general, but arguing against this idea is the observation that, as obesity rates increased, age at menarche didn't further decrease. That is, it's apparently not a simple matter of body size or nutritional intake.

The question of what has caused early periods prompted a group of researchers in Britain to look prospectively at a cohort of 3000 girls, including nutritional intake at age 3, 7 and 10. They identified a group of girls at birth in 1991 or 1992, and followed them up for about 13 years both by questionnaire and clinically. Early menarche was considered 12 years 8 months or younger, experienced by about half of the sample.

Girls with 'high' meat intake were eating 8 or more portions of meat per week at age 3 and 12 or more portions at age 7. Since early menarche has been associated with increased risk of breast cancer (the odds ratio is 1.5 - 2 times higher for women who started having periods at or before age 12 vs. women who started at 15 or older), the authors of the paper note that early menarche should be of concern. (But remember that 1.5 - 2 times a fairly low risk is not that high, and that, anyway, the comparison group, women who reached menarche at 15 or older has been a very small fraction of women for decades, at least in the developed world, and they perhaps were late for reasons that also protect against breast cancer, or at least may have different hormonal profiles. So whether this increased odds ratio is meaningful is up to you to decide.)In this large group of contemporary girls we have found a number of associations between dietary intakes throughout childhood and the occurrence of menarche. We have confirmed previous findings of higher energy intakes among girls reaching menarche earlier, reflecting their larger body size. We have also found evidence that intakes of meat and total and animal protein, and also possibly PUFA [polyunsaturated fatty acids] in early to mid-childhood may increase the chances of menarche by 12 years 8 months. However, we found no evidence that the chances of reaching menarche increased with higher total fat intakes, or reduced with higher intakes of fruit, vegetables or NSP. Unexpectedly, higher vegetable intakes at 3 years were associated with an increased chance of reaching menarche, although this may have reflected the positive association between meat and vegetable intakes at 3 years.

But could the meat/menarche association be due to confounders, variables that are associated with meat consumption and are the true explanation for the correlation? Things like ethnicity, socioeconomic status, mother's behavior during pregnancy, and so on, which would influence diet? The researchers controlled for some of these, but ethnicity was classified crudely as white/non-white, for example, and in the UK, as elsewhere, non-white can cover a lot of different diets, so that something else that rides along with meat could be the explanation instead. Kind of cooking oil, for example--we have absolutely no evidence that this is the case, but the point is that it's possible. Not to mention that high meat consumption is often associated with increased consumption of processed foods in general, which was not controlled for. That is, high meat consumption could indicate a different diet, with some unidentified causative variable, compared with the diet of kids who eat less meat.

Another possible confounding variable that has long been discussed in the literature--though as far as we can tell, the association is still only suggestive--is exogenous hormone levels in meat (a brief time out for a bow to the web, where you can find just about anything: here, for example, is a link to the "Museum of Menstruation and Women's Health", which we stumbled upon in searching for papers on meat hormones and age at menarche). Animals, of course, are given a panorama of hormones to increase the speed at which they grow. Whether these hormones are found in excess in meat, or are active in our bodies when we eat that meat isn't clear, at least to us. But it's certainly a possible alternative explanation for the association between meat consumption and age at menarche.

So, should we stop feeding meat to little girls? Early age at menarche, whatever its cause, may be a risk factor for breast cancer (any increased risk is not to be taken lightly, though see above), but it has also been found to protect against osteoporosis--both presumed to be due to the increased length of exposure to estrogen. And, of course age at menarche is by no means the only factor associated with risk of breast cancer or osteoporosis. And the protein and other ingredients in meat are likely good for other aspects of growth and health.

Of course epidemiologists (and journal editors) have to eat, and to do that they have to publish lots of studies! Does this study tell us anything of significance? You decide.

That soy and its offspring contain phyto-estrogens is known: that estrogen mimics might trigger early menarche is hardly a giant step, and asking questions about a food with such properties just might be Popperian.

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